ADT Dichotomy Confirmed For Intermediate-Risk Prostate Cancer Patients

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: The use of short-term androgen deprivation therapy (ADT) during radiotherapy offers significant survival benefits for men with unfavourable, but not favourable, intermediate-risk prostate cancer, confirms a secondary analysis of the RTOG 9408 trial.  

“[T]hese results are the highest quality to date supporting a dichotomization of intermediate-risk prostate cancer into favorable and unfavorable subgroups, and support National Comprehensive Cancer Network recommendations to limit ADT use [to] patients with [unfavourable intermediate-risk] disease”, the researchers write in JAMA Network Open. 

The randomised clinical trial compared survival outcomes for men given a 4-month course of ADT plus radiotherapy versus radiotherapy alone, explain Zachary Zumsteg, from Cedars-Sinai Medical Center in Los Angeles, California, USA, and co-authors. 

After a median 17.8 years of follow-up, the 513 patients with an unfavourable prognosis had significantly higher risk than the 377 favourable prognosis patients for distant metastases (hazard ratio [HR]=2.36), prostate cancer-specific mortality (PCSM, HR=1.84) and all-cause mortality (ACM, HR=1.19). 

Use of ADT among unfavourable prognosis patients significantly reduced the risk of distant metastases (HR=0.48) and PCSM (HR=0.40), albeit the reduction in the risk of ACM did not reach significance (HR=0.84). By contrast, use of ADT did not significantly alter the risk of any of these three endpoints among patients with a favourable prognosis. 

A 15-year restricted mean survival time analysis also significantly supported ADT use among patients with an unfavourable prognosis (10.5 vs 9.8 years), but found no significant benefit with ADT use among the favourable prognosis group (11.0 vs 10.7 years). 

“Notably, given Gleason score inflation, improvements in radiation delivery, and advances in imaging over the last 25 years, it is likely that ADT would have even less benefit to contemporary patients with [favourable intermediate-risk prostate cancer] than those enrolled in RTOG 9408”, the researchers remark. 

They add: “Future studies exploring genomic classifiers to further personalize therapy in intermediate-risk prostate cancer should be performed.” 

Reference 

Zumsteg ZS, Spratt DE, Daskivich TJ, et al. Effect of androgen deprivation on long-term outcomes of intermediate-risk prostate cancer stratified as favorable or unfavorable. A secondary analysis of the RTOG 9408 randomized clinical trial. JAMA Netw Open; 3: e2015083, published online 9 September 2020. doi:10.1001/jamanetworkopen.2020.15083.